Asymmetric catalytic hydrogenation is an area of intensive research within asymmetric synthesis. [Ohkuma, T.; Kitamura, M.; Noryori, R. (1999) Asymmetric Hydrogenation. In: Catalytic Asymmetric Synthesis, 2nd Ed. (Ed.: Ojima, I.). Wiley-VCH, New York, 2000], [The Handbook of Homogeneous Hydrogenation (Ed.: de Vries, J. G., Elsevier, C. J.). Wiley-VCH: Weinheim, 2007; Vol. 1-3.]. The efficiency and usefulness of the process is exemplified by several industrial applications so far developed. [Asymmetric Catalysis on Industrial Scale (Ed.: Blaser, H.-U.; Schmidt). Wiley-VCH, Weinheim, 2004].
Chiral alcohols are one of the important chiral compounds in the pharmaceutical, agrochemical and fine chemical industries, with asymmetric hydrogenation of ketone substrates the most effective way for the preparation of chiral alcohols. Noyori's research group have achieved the asymmetric hydrogenation of ketones by applying the concept of bifunctional catalysis in designing complexes of the type trans-RuCl2(diphosphane)(1,2-diamine). In the presence of bases like t-BuOK or KOH, these type of complexes can catalyse the asymmetric hydrogentation of simple ketone substrates with excellent enantioselectivity and catalytic efficiency. [Noyori, R.; Takeshi, O.; Hirohito, O. Shohei, H.; Takao, I. J. Am. Chem. Soc. 1995, 117, 2675], [Noyori, R.; Ohkuma, T.; Douce, H.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England, A. F.; Ikariya, T., Angew. Chem. Int. Ed. 1998, 37, 1703]. With various combinations of new design bidentate ligands, such complexes have been successfully used in the asymmetric hydrogenation of a wide range of ketone substrates. [Jing, W.; Hua, C.; Waihim, K.; Rongwei, G.; Zhongyuan, Z.; Chihung, Y.; Chan, A. S. C., J. Chem. Soc. 2002, 67, 7908], [Jing, W.; Jian, X.; Rongwei, G.; Chihung, Y.; Chan, S. C., Chem. Eur. J. 2003, 9, 2963], [Jian, H. X.; Xin, L. W.; Fu, Y.; Shuo, F. Z.; Bao, M. F.; Hai, F. D.; Zhou, Q. L. J. Am. Chem. Soc. 2003. 125, 4404], [Mark, J.; William, H.; Daniela, H.; Christophe, M.; Antonio, Z. G. Org. Lett. 2000, 26, 4173].
Recently Noyori's group has devised a new catalyst, RuCl2(phosphane)(α-picolylamine). By changing the diamine ligand to a hybrid amine ligand having structural motif of NH2—N(sp2), they can reduce ketones having a sterically bulky tert-butyl group on the α-position to the corresponding chiral secondary alcohol. This type of catalyst is by far the most active hydrogenation catalyst toward these particularly difficult ketone substrates. It is worth noting that the chiral tert-butyl alcohols are important for the preparation of some useful chiral surfactants. The common Ru complex of diphosphine-diamine type can only result in low conversion and low enantioselectivity (<20% e.e and conversion) in the reduction of these particular class of ketone substrates. [Ohkuma, T.; Sandoval, C. A.; Srinivasan, R.; Lin, Q.; Wei, Y.; Muñiz, K.; Noyori R. J. Am. Chem. Soc. 2005, 127, 8288.].
The major drawback for all aforementioned NH2-ligand containing catalyst systems is the necessary use of protonic solvents and basic conditions during the hydrogenation reaction. The employment of protonic solvents may limit the scope of ketone substrates being applied in this catalytic hydrogenation methodology due to solubility issues, and also unfavourably interact with additional functionalities when more elaborate substrates are involved. Furthermore the difficulties on accessing a wide range of vicinal chiral diamine ligands are another limitation for the preparation of such catalyst systems. After our systematic study on the mechanism of this ketone reduction using RuCl2(phosphane)(α-picolylamine or 1,2-diamine) as hydrogenation catalyst, we are able to design a new class of ruthenium complexes having a new hybrid NH2—N(sp2) structural motif as bidentate amine ligand that can catalyse the hydrogenation of simple aryl ketone in both aprotonic (eg. toluene, THF) and protonic solvents, in contrast to current catalyst system that only work in protonic solvents.